Myocardial and circulating levels of microRNA-21 reflect left ventricular fibrosis in aortic stenosis patients
Background: Various human cardiovascular pathophysiological conditions associate aberrant expression of microRNAs (miRNAs) and circulating miRNAs are emerging as promising biomarkers. In mice, myocardial miR-21 overexpression is related to cardiac fibrosis elicited by pressure overload. This study w...
| Autores: | , , , , , , , , |
|---|---|
| Tipo de recurso: | artículo |
| Fecha de publicación: | 2012 |
| País: | España |
| Institución: | Universidad de Cantabria (UC) |
| Repositorio: | UCrea Repositorio Abierto de la Universidad de Cantabria |
| Idioma: | inglés |
| OAI Identifier: | oai:repositorio.unican.es:10902/1127 |
| Acceso en línea: | http://hdl.handle.net/10902/1127 |
| Access Level: | acceso abierto |
| Palabra clave: | Aortic stenosis Myocardial fibrosis MicroRNA Plasma miR-21 TGF-β signaling |
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Myocardial and circulating levels of microRNA-21 reflect left ventricular fibrosis in aortic stenosis patientsVillar Ramos, Ana VictoriaGarcía López, RaquelMerino Fernández, DavidLlano Cardenal, MiguelCobo Belaustegui, ManuelMontalvo Silva, Cecilia deMartín Durán, RafaelHurlé González, María AmorNistal Herrera, Juan Francisco|||0000-0002-4152-7621Aortic stenosisMyocardial fibrosisMicroRNAPlasma miR-21TGF-β signalingBackground: Various human cardiovascular pathophysiological conditions associate aberrant expression of microRNAs (miRNAs) and circulating miRNAs are emerging as promising biomarkers. In mice, myocardial miR-21 overexpression is related to cardiac fibrosis elicited by pressure overload. This study was designed to determine the role of myocardial and plasmatic miR-21 in the maladaptive remodeling of the extracellular matrix induced by pressure overload in aortic stenosis (AS) patients and the clinical value of miR-21 as a biomarker for pathological myocardial fibrosis. Methods: In left ventricular biopsies from 75 AS patients and 32 surgical controls, we quantified the myocardial transcript levels of miR-21, miR-21-targets and ECM- and TGF-β-signaling-related elements. miR-21 plasma levels were determined in 25 healthy volunteers and in AS patients. In situ hybridization of miR-21 wasperformed in myocardial sections. Results: The myocardial and plasma levels of miR-21 were significantly higher in the AS patients compared with controls and correlated directly with the echocardiographic mean transvalvular gradients. miR-21 overexpression was confined to interstitial cells and absent in cardiomyocytes. Using bootstrap validated multiple linear regression, the variance in myocardial collagen expression was predicted by myocardial miR-21 (70% of collagen variance) or plasma miR-21 (52% of collagen variance), together with the miR-21 targets RECK and PDCD4, and effectors of TGF-β signaling. Conclusions: Our results support the role of miR-21 as a regulator of the fibrotic process that occurs in response to pressure overload in AS patients and underscore the value of circulating miR-21 as a biomarker for myocardial fibrosis.This work was supported by the Instituto de Salud Carlos III [PS09/01097], Ministerio de Ciencia e Innovación (SAF2010-16894), Fundación Marqués de Valdecilla Universidad de Cantabria [FMV-UC 09/01], and Instituto de Formación e Investigación Marqués de Valdecilla [FMV-API 10/20]ElsevierUniversidad de Cantabria20122012-08-08journal articlehttp://purl.org/coar/resource_type/c_6501NAhttp://purl.org/coar/version/c_be7fb7dd8ff6fe43info:eu-repo/semantics/articlehttp://hdl.handle.net/10902/1127International Journal of Cardiology, 2013, 167(6), 2875-81reponame:UCrea Repositorio Abierto de la Universidad de Cantabriainstname:Universidad de Cantabria (UC)Inglésengopen accesshttp://purl.org/coar/access_right/c_abf2info:eu-repo/semantics/openAccessoai:repositorio.unican.es:10902/11272026-06-02T12:39:31Z |
| dc.title.none.fl_str_mv |
Myocardial and circulating levels of microRNA-21 reflect left ventricular fibrosis in aortic stenosis patients |
| title |
Myocardial and circulating levels of microRNA-21 reflect left ventricular fibrosis in aortic stenosis patients |
| spellingShingle |
Myocardial and circulating levels of microRNA-21 reflect left ventricular fibrosis in aortic stenosis patients Villar Ramos, Ana Victoria Aortic stenosis Myocardial fibrosis MicroRNA Plasma miR-21 TGF-β signaling |
| title_short |
Myocardial and circulating levels of microRNA-21 reflect left ventricular fibrosis in aortic stenosis patients |
| title_full |
Myocardial and circulating levels of microRNA-21 reflect left ventricular fibrosis in aortic stenosis patients |
| title_fullStr |
Myocardial and circulating levels of microRNA-21 reflect left ventricular fibrosis in aortic stenosis patients |
| title_full_unstemmed |
Myocardial and circulating levels of microRNA-21 reflect left ventricular fibrosis in aortic stenosis patients |
| title_sort |
Myocardial and circulating levels of microRNA-21 reflect left ventricular fibrosis in aortic stenosis patients |
| dc.creator.none.fl_str_mv |
Villar Ramos, Ana Victoria García López, Raquel Merino Fernández, David Llano Cardenal, Miguel Cobo Belaustegui, Manuel Montalvo Silva, Cecilia de Martín Durán, Rafael Hurlé González, María Amor Nistal Herrera, Juan Francisco|||0000-0002-4152-7621 |
| author |
Villar Ramos, Ana Victoria |
| author_facet |
Villar Ramos, Ana Victoria García López, Raquel Merino Fernández, David Llano Cardenal, Miguel Cobo Belaustegui, Manuel Montalvo Silva, Cecilia de Martín Durán, Rafael Hurlé González, María Amor Nistal Herrera, Juan Francisco|||0000-0002-4152-7621 |
| author_role |
author |
| author2 |
García López, Raquel Merino Fernández, David Llano Cardenal, Miguel Cobo Belaustegui, Manuel Montalvo Silva, Cecilia de Martín Durán, Rafael Hurlé González, María Amor Nistal Herrera, Juan Francisco|||0000-0002-4152-7621 |
| author2_role |
author author author author author author author author |
| dc.contributor.none.fl_str_mv |
Universidad de Cantabria |
| dc.subject.none.fl_str_mv |
Aortic stenosis Myocardial fibrosis MicroRNA Plasma miR-21 TGF-β signaling |
| topic |
Aortic stenosis Myocardial fibrosis MicroRNA Plasma miR-21 TGF-β signaling |
| description |
Background: Various human cardiovascular pathophysiological conditions associate aberrant expression of microRNAs (miRNAs) and circulating miRNAs are emerging as promising biomarkers. In mice, myocardial miR-21 overexpression is related to cardiac fibrosis elicited by pressure overload. This study was designed to determine the role of myocardial and plasmatic miR-21 in the maladaptive remodeling of the extracellular matrix induced by pressure overload in aortic stenosis (AS) patients and the clinical value of miR-21 as a biomarker for pathological myocardial fibrosis. Methods: In left ventricular biopsies from 75 AS patients and 32 surgical controls, we quantified the myocardial transcript levels of miR-21, miR-21-targets and ECM- and TGF-β-signaling-related elements. miR-21 plasma levels were determined in 25 healthy volunteers and in AS patients. In situ hybridization of miR-21 wasperformed in myocardial sections. Results: The myocardial and plasma levels of miR-21 were significantly higher in the AS patients compared with controls and correlated directly with the echocardiographic mean transvalvular gradients. miR-21 overexpression was confined to interstitial cells and absent in cardiomyocytes. Using bootstrap validated multiple linear regression, the variance in myocardial collagen expression was predicted by myocardial miR-21 (70% of collagen variance) or plasma miR-21 (52% of collagen variance), together with the miR-21 targets RECK and PDCD4, and effectors of TGF-β signaling. Conclusions: Our results support the role of miR-21 as a regulator of the fibrotic process that occurs in response to pressure overload in AS patients and underscore the value of circulating miR-21 as a biomarker for myocardial fibrosis. |
| publishDate |
2012 |
| dc.date.none.fl_str_mv |
2012 2012-08-08 |
| dc.type.none.fl_str_mv |
journal article http://purl.org/coar/resource_type/c_6501 NA http://purl.org/coar/version/c_be7fb7dd8ff6fe43 |
| dc.type.openaire.fl_str_mv |
info:eu-repo/semantics/article |
| format |
article |
| dc.identifier.none.fl_str_mv |
http://hdl.handle.net/10902/1127 |
| url |
http://hdl.handle.net/10902/1127 |
| dc.language.none.fl_str_mv |
Inglés eng |
| language_invalid_str_mv |
Inglés |
| language |
eng |
| dc.rights.none.fl_str_mv |
open access http://purl.org/coar/access_right/c_abf2 |
| dc.rights.openaire.fl_str_mv |
info:eu-repo/semantics/openAccess |
| rights_invalid_str_mv |
open access http://purl.org/coar/access_right/c_abf2 |
| eu_rights_str_mv |
openAccess |
| dc.publisher.none.fl_str_mv |
Elsevier |
| publisher.none.fl_str_mv |
Elsevier |
| dc.source.none.fl_str_mv |
International Journal of Cardiology, 2013, 167(6), 2875-81 reponame:UCrea Repositorio Abierto de la Universidad de Cantabria instname:Universidad de Cantabria (UC) |
| instname_str |
Universidad de Cantabria (UC) |
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UCrea Repositorio Abierto de la Universidad de Cantabria |
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UCrea Repositorio Abierto de la Universidad de Cantabria |
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| repository.mail.fl_str_mv |
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1869412714095312896 |
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15,300724 |